PDF(Pubmed)
Abstract：
Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.
摘要：
慢性压力有助于发展抑郁症的风险;hu子，上丘脑的一个核,与许多神经精神疾病有关。使用全基因组基因表达分析，我们分析了暴露于慢性束缚应激14天的大鼠的hb的转录组。我们鉴定了379个受慢性应激影响的差异表达基因(DEGs)。这些基因富含神经活性配体-受体相互作用，环磷酸腺苷（cAMP）信号通路，昼夜节律夹带，和突触信号从京都百科全书的基因和基因组途径分析和响应皮质类固醇，脂质运输的正向调节，顺行跨突触信号，和来自基因本体论分析的化学突触传递。基于蛋白质-蛋白质相互作用网络分析的DEGs，我们确定了神经活性配体-受体相互作用，昼夜节律夹带，和胆碱能突触相关亚簇。此外,DEGs的细胞类型和a状区域表达，使用最近发表的单细胞RNA测序研究（GSE137478）进行评估，强烈表明，与神经活性配体-受体相互作用和跨突触信号相关的DEGs在内侧a神经元中高度富集。一起来看,我们的研究结果提供了一组有价值的分子靶标,这些靶标可能在介导对应激反应和慢性应激诱导的抑郁行为的发作中起重要作用.
